Homoharringtonine Plus Low-Dose Cytarabine in Treating Patients With Newly Diagnosed Chronic Myelogenous Leukemia in Chronic Phase

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00003694
First received: November 1, 1999
Last updated: June 4, 2013
Last verified: June 2013
  Purpose

Phase II trial to study the effectiveness of homoharringtonine plus low-dose cytarabine in treating patients who have newly diagnosed chronic phase chronic myelogenous leukemia. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.


Condition Intervention Phase
Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Chronic Phase Chronic Myelogenous Leukemia
Drug: omacetaxine mepesuccinate
Drug: cytarabine
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Newly Diagnosed Patients With BCR/ABL (+) Chronic Myelogenous Leukemia Treated With Combined Homoharringtonine (NSC #141633) and Low-Dose Cytarabine

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Complete cytogenetic, major cytogenetic, and hematologic response rate [ Time Frame: Up to 9 months ] [ Designated as safety issue: No ]
    Two separate single-stage Fleming designs will be used to test hypotheses regarding the major cytogenetic response rate and the complete cytogenetic response rate. Calculated and presented with their 95% confidence intervals.


Secondary Outcome Measures:
  • Toxicity rates as assessed by Common Terminology Criterial version 2.0 [ Time Frame: Up to 9 months ] [ Designated as safety issue: Yes ]
  • Duration of hematological response [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Described with Kaplan-Meier curves.

  • Time to hematological progression [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Described with Kaplan-Meier curves.


Enrollment: 60
Study Start Date: March 1999
Primary Completion Date: August 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (omacetaxine mepesuccinate, cytarabine)
Patients receive cytarabine and homoharringtonine concurrently by continuous intravenous infusion for 7 days. Courses repeat every 28 days. Patients receive a minimum of 9 courses of therapy in the absence of disease progression and unacceptable toxicity. Patients who are major cytogenetic responders at 9 months may continue therapy or switch to interferon. Minor cytogenetic responders are switched to interferon, and nonresponders are removed from therapy and given the option to switch to interferon.
Drug: omacetaxine mepesuccinate
Given IV
Other Names:
  • CGX-635
  • homoharringtonine
Drug: cytarabine
Given IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To estimate the hematologic and cytogenetic response rate of newly diagnosed patients with BCR/ABL (+) chronic myelogenous leukemia (CML) treated with combined homoharringtonine (omacetaxine mepesuccinate) and low dose cytarabine.

II. To estimate the toxicity of these two drugs given in combination in a cooperative group setting.

SECONDARY OBJECTIVES:

I. To assess duration of hematological response and incidence of hematological progression for all patients.

II. To assess duration of cytogenetic response in patients continuing protocol therapy beyond the initial nine months.

III. To use quantitative Southern blot monitoring of blood samples to monitor molecular response rates in patients entered onto CALGB treatment studies for CML.

IV. To compare quantitative Southern blot results of blood samples with marrow cytogenetics at the time of complete molecular response.

V. To use RT-PCR to monitor the frequency of residual disease in patients who have achieved a complete blood Southern blot and marrow cytogenetic response (elimination of BCR/ABL positivity by Southern blot and absence of the Philadelphia chromosome by cytogenetics).

OUTLINE:

Patients receive cytarabine and homoharringtonine concurrently by continuous intravenous infusion for 7 days. Courses repeat every 28 days. Patients receive a minimum of 9 courses of therapy in the absence of disease progression and unacceptable toxicity. Patients who are major cytogenetic responders at 9 months may continue therapy or switch to interferon. Minor cytogenetic responders are switched to interferon, and nonresponders are removed from therapy and given the option to switch to interferon.

Patients are followed every 6 months for 10 years.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologic diagnosis of chronic myelogenous leukemia (CML) in chronic phase; patients in either accelerated or blastic phases are not eligible; clonal cytogenetic evolution alone does not exclude patients
  • Patients must meet one or more of the following criteria:

    • Cytogenetically determined Philadelphia chromosome (Ph+)
    • BCR/ABL protein detectable by immunoblotting
    • Polymerase chain reaction (PCR) positive fusion transcripts for BCR/ABL
    • BCR/ABL translocation present by fluorescence in situ hybridization (FISH)
  • Registration within eight weeks of the diagnosis and confirmation of Ph+ or BCR/ABL+ CML
  • No more than eight weeks of prior hydroxyurea therapy
  • No previous therapy with homoharringtonine (HHT)
  • No prior treatment for CML with agents other than hydroxyurea; thus, prior treatment for CML with agents such as interferon, busulfan or cytarabine will render patients ineligible
  • Must not be a candidate for an early allogeneic bone marrow transplant; potential transplant candidates must be counseled about alternative donor transplants and must decline that treatment option
  • ECOG performance status 0-2
  • Non-pregnant and non-nursing; treatment under this protocol would expose an unborn child to significant risks; women and men of reproductive potential should agree to use an effective means of birth control
  • Bilirubin =< x upper limit of normal
  • Creatinine =< 1.5 mg/dl
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003694

Locations
United States, Massachusetts
Dana-Farber Harvard Cancer Center
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Investigators
Principal Investigator: Richard Stone Cancer and Leukemia Group B
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00003694     History of Changes
Other Study ID Numbers: NCI-2012-02786, CALGB-19804, U10CA031946
Study First Received: November 1, 1999
Last Updated: June 4, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Cytarabine
Homoharringtonine
Harringtonines
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on July 29, 2014